Renal Cell Carcinoma
description
Transcript of Renal Cell Carcinoma
![Page 1: Renal Cell Carcinoma](https://reader036.fdocuments.net/reader036/viewer/2022062305/56816649550346895dd9c319/html5/thumbnails/1.jpg)
Renal Cell CarcinomaAbdulrahim Gari, MD
Consultant of Internal MedicineHematology and Oncology
www.garimedical.com02-2632099
![Page 2: Renal Cell Carcinoma](https://reader036.fdocuments.net/reader036/viewer/2022062305/56816649550346895dd9c319/html5/thumbnails/2.jpg)
• RCC accounts for 2% to 3% of all adult malignant , 85% of all primary malignant renal tumors, is the most lethal of the urologic cancers
• Renal cell carcinoma (RCC) affects 38,000 individuals in the U.S. yearly, and 11,900 patients die of this disease
• RCC occurs most commonly in 5th~6th decade, male-female ratio 1.6:1
Renal Cell Carcinoma (RCC)
![Page 3: Renal Cell Carcinoma](https://reader036.fdocuments.net/reader036/viewer/2022062305/56816649550346895dd9c319/html5/thumbnails/3.jpg)
Etiology
• Majority of RCC occurs sporadically• Tobacco smoking contributes to 24-30% of RCC cases - Tobacco results in a 2-fold increased risk • Occupational exposure to cadmium, asbestos, petroleum• Obesity• Chronic phenacetin or aspirin use • Acquired polycystic kidney disease due to dialysis results
in 30% increase risk
![Page 4: Renal Cell Carcinoma](https://reader036.fdocuments.net/reader036/viewer/2022062305/56816649550346895dd9c319/html5/thumbnails/4.jpg)
• 2-4% of RCC associated with inherited disorder * Von Hippel-Lindau disease - familial cancer syndrome of retinal angiomas, CNS
hemangioblastomas, pheochromocytomas and clear cell RCC. * Hereditary papillary renal cancer - Multiple, bilateral papillary renal tumors , C-met oncogene
on ch 7 * Birt-Hogg-Duke syndrome - Fibrofolliculomas, lung cysts, and RCC, Mutation in BHD
gene ch 17p
Etiology
![Page 5: Renal Cell Carcinoma](https://reader036.fdocuments.net/reader036/viewer/2022062305/56816649550346895dd9c319/html5/thumbnails/5.jpg)
Pathology• RCC originates from the
proximal renal tubular epithelium.
• Types:• Clear cell type• Granular cell type• Mixed cell type
• RCC is most often a mixed adenocarcinoma.
![Page 6: Renal Cell Carcinoma](https://reader036.fdocuments.net/reader036/viewer/2022062305/56816649550346895dd9c319/html5/thumbnails/6.jpg)
Clinical Findings
Symptoms & Signs Renal tumors are increasingly detected incidentally
by CT or ultrasound
A. Classical triad——gross hematuria, flank pain, palpable mass (only in 10~15% advanced cases)
• Symptoms secondary to metastatic disease: dysnea & cough, seizure & headache, bone pain
![Page 7: Renal Cell Carcinoma](https://reader036.fdocuments.net/reader036/viewer/2022062305/56816649550346895dd9c319/html5/thumbnails/7.jpg)
Clinical Findings
B. Paraneoplastic Syndromes• Erythrocytosis, hypercalcemia, hypertensionC. Lab Findings• anemia, hematuria (60%), ESR↑
![Page 8: Renal Cell Carcinoma](https://reader036.fdocuments.net/reader036/viewer/2022062305/56816649550346895dd9c319/html5/thumbnails/8.jpg)
Clinical Findings
B. Paraneoplastic Syndromes• Erythrocytosis, hypercalcemia, hypertensionC. Lab Findings• anemia, hematuria (60%), ESR↑
![Page 9: Renal Cell Carcinoma](https://reader036.fdocuments.net/reader036/viewer/2022062305/56816649550346895dd9c319/html5/thumbnails/9.jpg)
Clinical Findings
D. Imaging• Ultrasonography• Intravenous Urography (IVU): • CT scanning: more sensitive, mass+renal
hilum, perinephric space and vena cava, adrenals, regional LN and adjacent organs
• Renal Angiography• MRI: to evaluate collecting system and IVC
involvement
![Page 10: Renal Cell Carcinoma](https://reader036.fdocuments.net/reader036/viewer/2022062305/56816649550346895dd9c319/html5/thumbnails/10.jpg)
Diagnosis
• No screening for the general population• No bio-marker available• Radiographic evaluation
![Page 11: Renal Cell Carcinoma](https://reader036.fdocuments.net/reader036/viewer/2022062305/56816649550346895dd9c319/html5/thumbnails/11.jpg)
IVU of right RCC
CT Scan of Left RCC
![Page 12: Renal Cell Carcinoma](https://reader036.fdocuments.net/reader036/viewer/2022062305/56816649550346895dd9c319/html5/thumbnails/12.jpg)
RCC invading renal vein
Right Cystic RCC
![Page 13: Renal Cell Carcinoma](https://reader036.fdocuments.net/reader036/viewer/2022062305/56816649550346895dd9c319/html5/thumbnails/13.jpg)
CT scan with 3D reconstructionNeovascularity in Renal
Angiographyassociated with RCC
![Page 14: Renal Cell Carcinoma](https://reader036.fdocuments.net/reader036/viewer/2022062305/56816649550346895dd9c319/html5/thumbnails/14.jpg)
A, Magnetic resonance scan of kidneys without administration of gadolinium suggests anterior right
renal mass.
B, After intravenous administration of gadolinium-labeled
diethylenetriaminepentaacetic acid, MRI shows enhancement of this mass
indicative of malignancy.
![Page 15: Renal Cell Carcinoma](https://reader036.fdocuments.net/reader036/viewer/2022062305/56816649550346895dd9c319/html5/thumbnails/15.jpg)
Tissue Diagnosis
• Tissue diagnosis obtained from nephrectomy or biopsy
Papillary (chromophilic) renal cell carcinoma extending into the collecting
system with histological findings
![Page 16: Renal Cell Carcinoma](https://reader036.fdocuments.net/reader036/viewer/2022062305/56816649550346895dd9c319/html5/thumbnails/16.jpg)
Tumor Staging (Robson System)
![Page 17: Renal Cell Carcinoma](https://reader036.fdocuments.net/reader036/viewer/2022062305/56816649550346895dd9c319/html5/thumbnails/17.jpg)
Tumor Staging (International TNM Staging System)
![Page 18: Renal Cell Carcinoma](https://reader036.fdocuments.net/reader036/viewer/2022062305/56816649550346895dd9c319/html5/thumbnails/18.jpg)
Tumor Staging
![Page 19: Renal Cell Carcinoma](https://reader036.fdocuments.net/reader036/viewer/2022062305/56816649550346895dd9c319/html5/thumbnails/19.jpg)
Differential Diagnosis
• Benign renal tumors -Angiomyolipoma
• Renal Pelvis Cancer
![Page 20: Renal Cell Carcinoma](https://reader036.fdocuments.net/reader036/viewer/2022062305/56816649550346895dd9c319/html5/thumbnails/20.jpg)
TreatmentA. Localized disease:• Surgical removal---only potentially curative therapy
• Radical Nephrectomy (en bloc removal of the kidney and Gerota’s fascia including ipsilateral adrenal, proximal ureter, regional lymphadenectomy
![Page 21: Renal Cell Carcinoma](https://reader036.fdocuments.net/reader036/viewer/2022062305/56816649550346895dd9c319/html5/thumbnails/21.jpg)
Laparoscopic Radical NephrectomyHand-Assisted Laparoscopic
Radical Nephrectomy
![Page 22: Renal Cell Carcinoma](https://reader036.fdocuments.net/reader036/viewer/2022062305/56816649550346895dd9c319/html5/thumbnails/22.jpg)
TreatmentA. Localized disease:• Partial Nephrectomy(nephron-sparing surgery, NSS ) --polar tumor --tumor size<4cm --bilateral RCC --solitary kidney
Laparoscopic NSS
![Page 23: Renal Cell Carcinoma](https://reader036.fdocuments.net/reader036/viewer/2022062305/56816649550346895dd9c319/html5/thumbnails/23.jpg)
TreatmentA. Localized disease:• Percutaneous/
Laparoscopic Radiofrequency Ablation or Cryoablation
Laparoscopic Cryoablation
![Page 24: Renal Cell Carcinoma](https://reader036.fdocuments.net/reader036/viewer/2022062305/56816649550346895dd9c319/html5/thumbnails/24.jpg)
Prognosis
• Stage 5-year survival rate • I 88~100%• II 60%• III 15~20%• IV 0~20%
![Page 25: Renal Cell Carcinoma](https://reader036.fdocuments.net/reader036/viewer/2022062305/56816649550346895dd9c319/html5/thumbnails/25.jpg)
Treatment
B. Disseminated disease:• nephrectomy--- reducing tumor burden• radiation--- radioresistant tumor, metastases 2/3
effective• chemotherapy--- <10% effective• immunotherapy--- IL-2/interferon-alpha, 30% response
rate• molecular therapy---eg. sorafenib
![Page 26: Renal Cell Carcinoma](https://reader036.fdocuments.net/reader036/viewer/2022062305/56816649550346895dd9c319/html5/thumbnails/26.jpg)
Interferons• They have antiviral, antiproliferative, and immunomodulatory
properties.• They have a antiproliferative effect on renal tumor cells in vitro• They stimulate host mononuclear cells, and enhance expression of
major histocompatibility complex molecules. • Interferon alfa, which is derived from leukocytes, has an objective
response rate of approximately 15% (range, 0-29%). • Preclinical studies have shown synergy between interferons and
cytotoxic drugs. • However, in several prospective randomized trials, combinations do
not appear to provide major advantages over single-agent therapy. • Many different types and preparations of interferons have been used
without any difference in efficacy.
![Page 27: Renal Cell Carcinoma](https://reader036.fdocuments.net/reader036/viewer/2022062305/56816649550346895dd9c319/html5/thumbnails/27.jpg)
Interleukin-2 immunotherapy
• High-dose IL-2 for robust patients with excellent cardiopulmonary reserve
• This remains the only treatment known to induce complete and durable remissions although in a minority of patients
• Studies are under way to identify patients responding to IL-2
![Page 28: Renal Cell Carcinoma](https://reader036.fdocuments.net/reader036/viewer/2022062305/56816649550346895dd9c319/html5/thumbnails/28.jpg)
IL2 +/- LAK in RCC
Law et al., Cancer 1995;76:824
![Page 29: Renal Cell Carcinoma](https://reader036.fdocuments.net/reader036/viewer/2022062305/56816649550346895dd9c319/html5/thumbnails/29.jpg)
AE of IL2
• Therapy requires inpatient monitoring, often in an intensive care unit.
• The major toxic effect of high-dose IL-2 is a sepsislike syndrome with decrease in systemic vascular resistance and an associated decrease in intravascular volume due to capillary leak.
• Other toxic effects are fever, chills, fatigue, infection, and hypotension.
• Only to patients with no cardiac ischemia or significant impairment of renal or pulmonary functions.
![Page 30: Renal Cell Carcinoma](https://reader036.fdocuments.net/reader036/viewer/2022062305/56816649550346895dd9c319/html5/thumbnails/30.jpg)
Bevacizumab + INF in RCC
PFS was shown in: Lancet 2007;370:2103
Escudier et al., JCO 2010;28:2144
![Page 31: Renal Cell Carcinoma](https://reader036.fdocuments.net/reader036/viewer/2022062305/56816649550346895dd9c319/html5/thumbnails/31.jpg)
Newer Targeted Therapy
![Page 32: Renal Cell Carcinoma](https://reader036.fdocuments.net/reader036/viewer/2022062305/56816649550346895dd9c319/html5/thumbnails/32.jpg)
Sorafenib
• Sorafenib, a small-molecule targets RAF, VEGF, PDGFR-beta, KIT, FLT-3
• Dose is 400 mg bid away from meals.• Interruptions or dose reductions because of AE
![Page 33: Renal Cell Carcinoma](https://reader036.fdocuments.net/reader036/viewer/2022062305/56816649550346895dd9c319/html5/thumbnails/33.jpg)
Sorafenib in RCC
Escudier et al., JCO 2009;27:3312
![Page 34: Renal Cell Carcinoma](https://reader036.fdocuments.net/reader036/viewer/2022062305/56816649550346895dd9c319/html5/thumbnails/34.jpg)
AE of Sorafenib • reversible skin rashes in 40%• hand-foot skin reaction in 30% (grade 3 and 4 in 5%)• diarrhea was reported in 43%• treatment-emergent hypertension in 17%• sensory neuropathic changes in 13%• were also reported more commonly in the sorafenib arm. • treatment-emergent cardiac ischemia/infarction events 2.9%
(placebo 0.4%)• asymptomatic hypophosphatemia in 45%• lipase elevations in 41%• Others: alopecia, oral mucositis, and hemorrhage, pancreatitis,
hypothyroidism
![Page 35: Renal Cell Carcinoma](https://reader036.fdocuments.net/reader036/viewer/2022062305/56816649550346895dd9c319/html5/thumbnails/35.jpg)
Sunitinib
• Sunitinib is multikinase inhibitor • High response rate (40% partial responses),
TTP of 8.7 months, and OS of 16.4 months. • Sunitinib inhibits tyrosine kinases in VEGFR 1-
3 and PDGFR-alpha and –beta pathways• Dose of sunitinib is 50 mg po od, with or
without food, 4 weeks on & 2 weeks off
![Page 36: Renal Cell Carcinoma](https://reader036.fdocuments.net/reader036/viewer/2022062305/56816649550346895dd9c319/html5/thumbnails/36.jpg)
Sunitinib in RCC
Motzer et al., JCO 2009;27:3584
![Page 37: Renal Cell Carcinoma](https://reader036.fdocuments.net/reader036/viewer/2022062305/56816649550346895dd9c319/html5/thumbnails/37.jpg)
AE of Sunitinib• fatigue (38%)• hypothyroidism (in as many as 30%)• diarrhea (24%)• nausea (19%)• dyspepsia (16%)• stomatitis (19%)• decline in cardiac ejection fraction (11%)• dermatitis in 8%• hypertension in 5% (but correlates with response,
DFS and OS)
![Page 38: Renal Cell Carcinoma](https://reader036.fdocuments.net/reader036/viewer/2022062305/56816649550346895dd9c319/html5/thumbnails/38.jpg)
Temsirolimus in RCC
• Temsirolimus inhibits mTOR (important in cell growth and division)
• hypoxia-inducible factor (HIF) pathway are also upregulated by mTOR
• This pathway is central in pathogenesis of kidney cancers.
• Dose 25 mg IV weekly until progression. • Common toxicities: asthenia, rash, anemia,
hypophosphatemia, hyperlipidemia.
![Page 39: Renal Cell Carcinoma](https://reader036.fdocuments.net/reader036/viewer/2022062305/56816649550346895dd9c319/html5/thumbnails/39.jpg)
Temsirolimus in RCC, PFS
Hudes et al., NEJM 2007;356:2271
![Page 40: Renal Cell Carcinoma](https://reader036.fdocuments.net/reader036/viewer/2022062305/56816649550346895dd9c319/html5/thumbnails/40.jpg)
Temsirolimus in RCC, OS
Hudes et al., NEJM 2007;356:2271
Temsirolimus vs INF:HR for death 0.73(CI 0.58-0.92)P <0.008
Combination vs INF:HR 0.96(CI 0.76-1.20)P <0.70
![Page 41: Renal Cell Carcinoma](https://reader036.fdocuments.net/reader036/viewer/2022062305/56816649550346895dd9c319/html5/thumbnails/41.jpg)
2nd line Everolimus in RCC
• Everolimus mTOR (important in cell growth and division)
• Dose is 10 mg po od with or without food• Approved as 2nd line after sunitinib and/or sorafenib• Tablets should be swallowed whole, not be chewed or
crushed, with a glass of water• Common toxicities: stomatitis, infections, asthenia,
fatigue, cough, and diarrhea
![Page 42: Renal Cell Carcinoma](https://reader036.fdocuments.net/reader036/viewer/2022062305/56816649550346895dd9c319/html5/thumbnails/42.jpg)
2nd line Everolimus in RCC PFS by central radiology review
Motzer et al., Cancer 2010;116:4256
![Page 43: Renal Cell Carcinoma](https://reader036.fdocuments.net/reader036/viewer/2022062305/56816649550346895dd9c319/html5/thumbnails/43.jpg)
Axitinib in RCC• Multicenter randomised phase 3 study comparing axitinib with sorafenib as
second-line therapy in metastatic RCC.• Patients randomly assigned (1:1) to either axitinib (5 mg twice daily) or
sorafenib (400 mg twice daily). • PFS was 6·7 months with axitinib compared to 4·7 months with sorafenib
(hazard ratio 0·665; CI 0·544-0·812; p<0·0001) • Treatment was discontinued because of toxic effects in 14 (4%) of 359 patients
treated with axitinib and 29 (8%) of 355 patients treated with sorafenib. • AE of axitinib were diarrhoea, hypertension, and fatigue• AE of sorafenib were diarrhoea, palmar-plantar erythrodysaesthesia, and
alopecia• Conclusion: Axitinib had significantly longer PFS compared with sorafenib.
Axitinib is a treatment option for second-line therapy of advanced renal cell carcinoma.
![Page 44: Renal Cell Carcinoma](https://reader036.fdocuments.net/reader036/viewer/2022062305/56816649550346895dd9c319/html5/thumbnails/44.jpg)
1st line Targeted Therapy of RCC
• For naïve patients with CC-RCC of low or intermediate risk, sunitinib or bevacizumab and IFN-alfa.
• For naïve patients with CC-RCC of high-risk temsirolimus
• Pazopanib for relapsed or unresectable CC-RCC of high-risk
• In separate trials following drugs are more effective than IFN-alpha as 1st line therapy for mRCC: sunitinib, bevacizumab plus IFN-alpha , and temsirolimus in terms of PFS or OS or both
![Page 45: Renal Cell Carcinoma](https://reader036.fdocuments.net/reader036/viewer/2022062305/56816649550346895dd9c319/html5/thumbnails/45.jpg)
2nd line Targeted Therapy of RCC
• 2nd line for CC-RCC sorafenib: standard dose, then increased dose
• Everolimus is approved as 2nd line after sunitinib and/or sorafenib
• For sunitinib naïve this drug can be used as 2nd line
![Page 46: Renal Cell Carcinoma](https://reader036.fdocuments.net/reader036/viewer/2022062305/56816649550346895dd9c319/html5/thumbnails/46.jpg)
Thank You
![Page 47: Renal Cell Carcinoma](https://reader036.fdocuments.net/reader036/viewer/2022062305/56816649550346895dd9c319/html5/thumbnails/47.jpg)
AE of Sorafenib
5% ischaemic /infarct in study group